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Contribution of antibody-dependent enhancement to the pathogenesis of coronavirus infections

  • Received: 12 June 2020 Accepted: 28 August 2020 Published: 03 September 2020
  • Since the emergence of the SARS-CoV-2 virus in late 2019, vaccines against the COVID-19 infection have been under development using different approaches. At present, protective immunity factors against COVID-19 infection are not completely characterized. Of the four structural proteins of coronavirus, the spike protein (S) and the nucleocapsid protein (N) are most widely expressed in viral infections and elicit the antibody response. Antibody-dependent enhancement (ADE) presents a problem for developing a vaccine against SARS-CoV. It was shown in animal studies that SARS-CoV-1 vaccines containing recombinant S-protein or DNA-vaccine expressed S-protein led to pulmonary immunopathology after infection with SARS virus. Antibodies to the coronavirus S-protein produced by the human immune system in response to infection may contribute to the penetration of SARS-CoV into monocytes and macrophages through the Fc-gamma receptor (FcγR) and may aggravate the course of infection. The demonstration of ADE with coronavirus infection raises fundamental questions regarding the development of vaccines against the SARS-CoV-2 virus and the use of passive prophylaxis or treatment with virus-specific monoclonal antibodies. Evaluation of the mechanisms of immunopathology, including the responses of immunoglobulins and cytokines to vaccines, and tests for antigen-antibody complexes after infection and vaccination can help address these issues.

    Citation: Yu. A. Desheva, A. S. Mamontov, P. G. Nazarov. Contribution of antibody-dependent enhancement to the pathogenesis of coronavirus infections[J]. AIMS Allergy and Immunology, 2020, 4(3): 50-59. doi: 10.3934/Allergy.2020005

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  • Since the emergence of the SARS-CoV-2 virus in late 2019, vaccines against the COVID-19 infection have been under development using different approaches. At present, protective immunity factors against COVID-19 infection are not completely characterized. Of the four structural proteins of coronavirus, the spike protein (S) and the nucleocapsid protein (N) are most widely expressed in viral infections and elicit the antibody response. Antibody-dependent enhancement (ADE) presents a problem for developing a vaccine against SARS-CoV. It was shown in animal studies that SARS-CoV-1 vaccines containing recombinant S-protein or DNA-vaccine expressed S-protein led to pulmonary immunopathology after infection with SARS virus. Antibodies to the coronavirus S-protein produced by the human immune system in response to infection may contribute to the penetration of SARS-CoV into monocytes and macrophages through the Fc-gamma receptor (FcγR) and may aggravate the course of infection. The demonstration of ADE with coronavirus infection raises fundamental questions regarding the development of vaccines against the SARS-CoV-2 virus and the use of passive prophylaxis or treatment with virus-specific monoclonal antibodies. Evaluation of the mechanisms of immunopathology, including the responses of immunoglobulins and cytokines to vaccines, and tests for antigen-antibody complexes after infection and vaccination can help address these issues.


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    Acknowledgments



    The authors thank Maria Kozlova for English editing.

    Conflict of interests



    All authors declare no conflicts of interest in this paper.

    [1] Diamond MS, Pierson TC (2020) The challenges of vaccine development against a new virus during a pandemic. Cell Host Microbe 27: 699-703. doi: 10.1016/j.chom.2020.04.021
    [2] Corey L, Mascola JR, Fauci AS, et al. (2020) A strategic approach to COVID-19 vaccine R&D. Science 368: 948-950. doi: 10.1126/science.abc5312
    [3] Corman VM, Muth D, Niemeyer D, et al. (2018) Hosts and sources of endemic human coronaviruses. Advances in Virus Research Cambridge: Academic Press, 163-188. doi: 10.1016/bs.aivir.2018.01.001
    [4] van Elden LJ, Anton M AM, van Alphen F, et al. (2004) Frequent detection of human coronaviruses in clinical specimens from patients with respiratory tract infection by use of a novel real-time reverse-transcriptase polymerase chain reaction. J Infect Dis 189: 652-657. doi: 10.1086/381207
    [5] Holmes KV (1999) Coronaviruses (Coronaviridae). Encyclopedia of Virology Cambridge: Academic Press, 291. doi: 10.1006/rwvi.1999.0055
    [6] Dijkman R, Jebbink MF, El Idrissi NB, et al. (2008) Human coronavirus NL63 and 229E seroconversion in children. J Clin Microbiol 46: 2368-2373. doi: 10.1128/JCM.00533-08
    [7] Peiris JS, Lai ST, Poon LL, et al. (2003) Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361: 1319-1325. doi: 10.1016/S0140-6736(03)13077-2
    [8] Arabi Y, Arifi A, Balkhy H, et al. (2014) Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med 160: 389-397. doi: 10.7326/M13-2486
    [9] Cha RH, Joh JS, Jeong I, et al. (2015) Renal complications and their prognosis in Korean patients with Middle East respiratory syndrome-coronavirus from the central MERS-CoV designated hospital. J Korean Med Sci 30: 1807-1814. doi: 10.3346/jkms.2015.30.12.1807
    [10] Saad M, Omrani AS, Baig K, et al. (2014) Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis 29: 301-306. doi: 10.1016/j.ijid.2014.09.003
    [11] Baig AM (2020) Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther 26: 499-501. doi: 10.1111/cns.13372
    [12] Raj VS, Mou H, Smits SL, et al. (2013) Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495: 251-254. doi: 10.1038/nature12005
    [13] Maslow JN (2017) Vaccine development for emerging virulent infectious diseases. Vaccine 35: 5437-5443. doi: 10.1016/j.vaccine.2017.02.015
    [14] Oh MD, Choe PG, Oh HS, et al. (2015) Middle East respiratory syndrome coronavirus superspreading event involving 81 persons, Korea 2015. J Korean Med Sci 30: 1701-1705. doi: 10.3346/jkms.2015.30.11.1701
    [15] Gerdts V, Zakhartchouk A (2017) Vaccines for porcine epidemic diarrhea virus and other swine coronaviruses. Vet Microbiol 206: 45-51. doi: 10.1016/j.vetmic.2016.11.029
    [16] de Wit JJS, Cook JKA (2019) Spotlight on avian pathology: infectious bronchitis virus. Avian Pathol 48: 393-395. doi: 10.1080/03079457.2019.1617400
    [17] Luo A (2020) Positive SARS-Cov-2 test in a woman with COVID-19 at 22 days after hospital discharge: A case report. J Tradit Chin Med Sci In press.
    [18] Fu W, Chen Q, Wang T (2020) Letter to the Editor: Three cases of re‐detectable positive SARS‐CoV‐2 RNA in recovered COVID‐19 patients with antibodies. J Med Virol In press.
    [19] Li G, Fan Y, Lai Y, et al. (2020) Coronavirus infections and immune responses. J Med Virol 92: 424-432. doi: 10.1002/jmv.25685
    [20] Li CK, Wu H, Yan H, et al. (2008) T cell responses to whole SARS coronavirus in humans. J Immunol 181: 5490-5500. doi: 10.4049/jimmunol.181.8.5490
    [21] Zhao J, Zhao J, Mangalam AK, et al. (2016) Airway memory CD4+ T cells mediate protective immunity against emerging respiratory coronaviruses. Immunity 44: 1379-1391. doi: 10.1016/j.immuni.2016.05.006
    [22] Prompetchara E, Ketloy C, Palaga T (2020) Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol 38: 1-9.
    [23] Lurie N, Saville M, Hatchett R, et al. (2020) Developing Covid-19 vaccines at pandemic speed. New Engl J Med 382: 1969-1973. doi: 10.1056/NEJMp2005630
    [24] de Haan CA, Rottier PJ (2005) Molecular interactions in the assembly of coronaviruses. Adv Virus Res 64: 165-230. doi: 10.1016/S0065-3527(05)64006-7
    [25] Baruah V, Bose S (2020) Immunoinformatics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV. J Med Virol 92: 495-500. doi: 10.1002/jmv.25698
    [26] Yang ZY, Kong WP, Huang Y, et al. (2004) A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 428: 561-564. doi: 10.1038/nature02463
    [27] Deming D, Sheahan T, Heise M, et al. (2006) Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med 3: e525. doi: 10.1371/journal.pmed.0030525
    [28] Graham RL, Becker MM, Eckerle LD, et al. (2012) A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nat Med 18: 1820. doi: 10.1038/nm.2972
    [29] Liu W, Fontanet A, Zhang PH, et al. (2006) Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome. J Infect Dis 193: 792-795. doi: 10.1086/500469
    [30] Tang F, Quan Y, Xin ZT, et al. (2011) Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. J Immunol 186: 7264-7268. doi: 10.4049/jimmunol.0903490
    [31] Boonnak K, Slike BM, Burgess TH, et al. (2008) Role of dendritic cells in antibody-dependent enhancement of dengue virus infection. J Virol 82: 3939-3951. doi: 10.1128/JVI.02484-07
    [32] Murphy BR, Prince GA, Walsh EE, et al. (1986) Dissociation between serum neutralizing and glycoprotein antibody responses of infants and children who received inactivated respiratory syncytial virus vaccine. J Clin Microbiol 24: 197-202. doi: 10.1128/JCM.24.2.197-202.1986
    [33] Taylor A, Foo SS, Bruzzone R, et al. (2015) Fc receptors in antibody‐dependent enhancement of viral infections. Immunol Rev 268: 340-364. doi: 10.1111/imr.12367
    [34] Winarski KL, Tang J, Klenow L, et al. (2019) Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics. Proc Natl Acad Sci USA 116: 15194-15199. doi: 10.1073/pnas.1821317116
    [35] Jaume M, Yip MS, Cheung CY, et al. (2011) Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH-and cysteine protease-independent FcγR pathway. J Virol 85: 10582-10597. doi: 10.1128/JVI.00671-11
    [36] Wang SF, Tseng SP, Yen CH, et al. (2014) Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins. Biochem Bioph Res Co 451: 208-214. doi: 10.1016/j.bbrc.2014.07.090
    [37] Kam YW, Kien F, Roberts A, et al. (2006) Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcRII-dependent entry into B cells in vitro. Vaccine 25: 729-740. doi: 10.1016/j.vaccine.2006.08.011
    [38] Wan Y, Shang J, Sun S, et al. (2020) Molecular mechanism for antibody-dependent enhancement of coronavirus entry. J Virol 94.
    [39] Dijstelbloem HM, Kallenberg CG, van de Winkel JG (2001) Inflammation in autoimmunity: receptors for IgG revisited. Trends Immunol 22: 510-516. doi: 10.1016/S1471-4906(01)02014-2
    [40] Baudino L, Nimmerjahn F, da Silveira SA, et al. (2008) Differential contribution of three activating IgG Fc receptors (FcγRI, FcγRIII, and FcγRIV) to IgG2a-and IgG2b-induced autoimmune hemolytic anemia in mice. J Immunol 180: 1948-1953. doi: 10.4049/jimmunol.180.3.1948
    [41] Jacobs JJ (2020) Neutralizing antibodies mediate virus-immune pathology of COVID-19. Med Hypotheses 30: 109884. doi: 10.1016/j.mehy.2020.109884
    [42] Wang S, Guo F, Liu K, et al. (2008) Endocytosis of the receptor-binding domain of SARS-CoV spike protein together with virus receptor ACE2. Virus Res 136: 8-15. doi: 10.1016/j.virusres.2008.03.004
    [43] Huang IC, Bosch BJ, Li F, et al. (2006) SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J Biol Chem 281: 3198-3203. doi: 10.1074/jbc.M508381200
    [44] Yip MS, Leung NH, Cheung CY, et al. (2014) Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus. Virol J 11: 82. doi: 10.1186/1743-422X-11-82
    [45] Yuan FF, Tanner J, Chan PK, et al. (2005) Influence of FcγRIIA and MBL polymorphisms on severe acute respiratory syndrome. Tissue Antigens 66: 291-296. doi: 10.1111/j.1399-0039.2005.00476.x
    [46] Quinlan BD, Mou H, Zhang L, et al. (2020) The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement. Immunity In press.
    [47] de Wit E, van Doremalen N, Falzarano D, et al. (2016) SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 14: 523. doi: 10.1038/nrmicro.2016.81
    [48] Tseng CT, Sbrana E, Iwata-Yoshikawa N, et al. (2012) Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PloS One 7: e35421. doi: 10.1371/journal.pone.0035421
    [49] Deming D, Sheahan T, Heise M, et al. (2006) Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med 3: e525. doi: 10.1371/journal.pmed.0030525
    [50] Bolles M, Deming D, Long K, et al. (2011) A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J Virol 85: 12201-12215. doi: 10.1128/JVI.06048-11
    [51] Liu L, Wei Q, Lin Q, et al. (2019) Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 4.
    [52] Pinto D, Park YJ, Beltramello M, et al. (2020) Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature 18: 1-10.
    [53] Gao Q, Bao L, Mao H, et al. (2020) Development of an inactivated vaccine candidate for SARS-CoV-2. Science 369: 77-81. doi: 10.1126/science.abc1932
    [54] van Doremalen N, Lambe T, Spencer A, et al. (2020) ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature 30: 1-8.
    [55] Corbett KS, Flynn B, Foulds KE, et al. (2020) Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. New Engl J Med In press.
    [56] Zhang L, Zhang F, Yu W, et al. (2006) Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals. J Med Virol 78: 1-8. doi: 10.1002/jmv.20499
    [57] Ho MS, Chen WJ, Chen HY, et al. (2005) Neutralizing antibody response and SARS severity. Emerg Infect Dis 11: 1730. doi: 10.3201/eid1111.040659
    [58] Lee N, Chan PK, Ip M, et al. (2006) Anti-SARS-CoV IgG response in relation to disease severity of severe acute respiratory syndrome. J Clin Virol 35: 179-184. doi: 10.1016/j.jcv.2005.07.005
    [59] To KK, Tsang OT, Leung WS, et al. (2020) Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis 5: 565-574.
    [60] Huang J, Mao T, Li S, et al. (2020) Dynamics of Viral Load and Antibodies in First 8 Weeks of Infection by SARS-CoV-2: An Observational Cohort Study. Lancet In press.
    [61] Cheng Y, Wong R, Soo Y, et al. (2005) Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 24: 44-46. doi: 10.1007/s10096-004-1271-9
    [62] Keith P (2020) A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care 24: 128. doi: 10.1186/s13054-020-2836-4
    [63] Liu Q, Zhou YH, Yang ZQ (2016) The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol 13: 3-10. doi: 10.1038/cmi.2015.74
    [64] Sullivan N, Yang ZY, Nabel GJ (2003) Ebola virus pathogenesis: implications for vaccines and therapies. J Virol 77: 9733-9737. doi: 10.1128/JVI.77.18.9733-9737.2003
    [65] Chen C, Zhang XR, Ju ZY, et al. (2020) Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies. Chinese J Burns 36: E005.
    [66] Schindewolf C, Menachery VD, et al. (2019) Middle east respiratory syndrome vaccine candidates: cautious optimism. Viruses 11: 74. doi: 10.3390/v11010074
    [67] Henderson LA, Canna SW, Schulert GS, et al. (2020) On the alert for cytokine storm: Immunopathology in COVID‐19. Arthritis Rheumatol 22: 1059-1063. doi: 10.1002/art.41285
    [68] Mehta P, McAuley DF, Brown M, et al. (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395: 1033-1034. doi: 10.1016/S0140-6736(20)30628-0
    [69] Huang C, Wang Y, Li X (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497-506. doi: 10.1016/S0140-6736(20)30183-5
    [70] Liu J, Li S, Liu J (2020) Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EbioMedicine 55: 102763. doi: 10.1016/j.ebiom.2020.102763
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